Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NFκB Mediated Signaling.

Ashraf Al Madhoun
* ORCID logo ,
Shihab Kochumon
,
Dania Haddad
ORCID logo ,
Reeby Thomas
ORCID logo ,
Rasheeba Nizam
ORCID logo ,
Lavina Miranda
,
Sardar Sindhu
ORCID logo ,
Milad S. Bitar
,
Rasheed Ahmad
* ORCID logo ,
Fahd Al-Mulla
* ORCID logo
Version 1 : Received: 11 December 2022 / Approved: 12 December 2022 / Online: 12 December 2022 (06:02:18 CET)

A peer-reviewed article of this Preprint also exists.

Al Madhoun, A.; Kochumon, S.; Haddad, D.; Thomas, R.; Nizam, R.; Miranda, L.; Sindhu, S.; Bitar, M.S.; Ahmad, R.; Al-Mulla, F. Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling. Cells 2023, 12, 1019. Al Madhoun, A.; Kochumon, S.; Haddad, D.; Thomas, R.; Nizam, R.; Miranda, L.; Sindhu, S.; Bitar, M.S.; Ahmad, R.; Al-Mulla, F. Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling. Cells 2023, 12, 1019.

Abstract

Obesity is characterized by chronic low-grade inflammation. Caveolin-1 (CAV1), a structural and functional protein found in adipose tissues (AT), is augmented in obese individuals. We aimed to define the inflammatory mediators that influence CAV1 gene regulation and associated mechanism in obesity. Using subcutaneous AT from 27 (7 lean/20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). CAV1 gene expression was associated with that of proinflammatory cytokines/chemokines, and their cognate receptor (r ≥ 0.447, p ≤ 0.030) but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-kB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and TNF-α signaling pathway is interesting and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Keywords

Caveolin 1; Obesity; Adipose tissue; Metabolic inflammation; Cytokines; TNF-α; NF-κB

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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